The Rad53 signal transduction pathway: Replication fork stabilization, DNA repair, and adaptation

Exp Cell Res. 2006 Aug 15;312(14):2654-9. doi: 10.1016/j.yexcr.2006.06.012. Epub 2006 Jun 20.


Cells are continually exposed to genomic insults resulting from exogenous and endogenous damage as well as by challenges posed by DNA replication. In order to maintain genome integrity, the cells must monitor and coordinate different aspects of chromosome metabolism with cell cycle events that are performed in a predetermined order. Checkpoints are cellular surveillance and signaling pathways that coordinate these physiological responses, and growing evidence suggests that failure of these controls can lead to profound genome instability and genetic disorders. In this review, we focus on the different types of signals and mechanisms that contribute to the budding yeast checkpoint activation, the role of the activated replication checkpoint in stabilizing replication forks and in assisting different types of DNA repair and fork restart mechanisms, as well as on the ability of cells to recover from checkpoint arrest after repairing the lesions or adapt when faced with unrepairable DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological*
  • Cell Cycle
  • Cell Cycle Proteins / metabolism*
  • Checkpoint Kinase 2
  • DNA Damage
  • DNA Repair*
  • DNA Replication*
  • DNA, Fungal
  • Protein-Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomycetales / genetics*
  • Signal Transduction


  • Cell Cycle Proteins
  • DNA, Fungal
  • Saccharomyces cerevisiae Proteins
  • Checkpoint Kinase 2
  • Protein-Serine-Threonine Kinases
  • RAD53 protein, S cerevisiae